In the Game Boy Advance game, different colored Yoshis can be found in question blocks on regular stages after finding each colored Yoshi on Star Road. Cape Mario/Cape Luigi can find a blue Yoshi, Fire Mario/Fire Luigi can find a red Yoshi, and Super Mario/Super Luigi and Small Mario/Small Luigi can find a yellow or green Yoshi. In the SNES game, only green Yoshis can be found in question blocks outside of Star Road and the Special World.

Ghost Houses and Fortresses do not have Dragon Coins on the SNES version, but appear in every level in the Game Boy Advance version. Because of this change, some level designs were reconfigured. The Dragon Coins will also turn into Peach Coins (after a cutscene) if all five Dragon Coins are collected in every single level in the Game Boy Advance game.

In the SNES version, enemy changes and Autumn-colored levels appear after completing the Special World. In the Game Boy Advance version, all 96 exits must be cleared instead.

Additionally, the Game Boy Advance version includes a cutscene showing Luigi in a balloon tossing out masks to the Koopas after unlocking the Autumn-colored levels, whereas the changes in the SNES version are first seen when entering Yoshi's house upon exiting the Special World.

Galoombas and Pokeys also have different appearances in the Game Boy Advance version, along with Koopas, Bullet Bills and Piranha plants like the SNES version.

In the SNES game, when Mario or Luigi gets hurt while having a power-up (i.e. fire flower or cape), Mario and Luigi will become Small Mario/Small Luigi, as they did in Super Mario Bros. In the Game Boy Advance game, Power-up Mario/Power-up Luigi will become Super Mario/Super Luigi when they are hurt, as they do in Super Mario Bros. 3. In both versions, if Super Mario/Super Luigi get hurt, the reserve item in the box at the top of the screen will drop down.

In the SNES version, the "Top Secret Area" stage is a yellow dot on the map. In the Game Boy Advance version, a smiling bush represents the stage.

In the SNES game, the timer for Bowser's Castle is 400 seconds; there is no time limit when fighting Bowser. In the Game Boy Advance game, the timer was increased to 800 seconds if entering through the front door and 600 seconds if entering from the back door due to the timer continues when fighting Bowser.

In the SNES game, the "Top Secret Area" stage does not have a timer. In the Game Boy Advance game, the "Top Secret Area" has 200 seconds on the timer.

A status menu is accessible on the world map by pressing the Select button on the Game Boy Advance version. The status menu allows the player to see total play time, score, the number of exits found by each brother, whether Princess Peach has been saved, and whether all of Dragon coins have been collected.

After completing all exits on every level, a stage select screen will also become available that will take the player to any chosen level.

In the SNES game, the maximum number of lives a player could have is 99. In the Game Boy Advance game, this was changed to 999.

The international version has several changes to levels when compared to the Japanese release. These include minor graphical changes to fix mistakes or to provide more obvious information to the player, along with several changes to make the game slightly easier.
These changes are also present in the Game Boy Advance release.

In the SNES release, Yoshi's house has seven berries on it. In the Game Boy Advance release, there are ten berries.

In an early prototype of the game, the clouds in the sky are reminiscent of old Japanese art. The world it overlooks is a mushroom shape, which resembles the prototype overworld. It would later appear in the Super Mario Advance version of the game.

In the Japanese version, Yoshi can eat the dolphins. This was removed from the international release. It's thought it was removed because of the different cultural views towards dolphins, or simply to make the level easier to finish, as the dolphins can be used as platforms. This was added back into all versions of the Game Boy Advance version.